Watarai Hikaru, Okada Masashi, Kuramoto Kenta, Takeda Hiroyuki, Sakaki Hirotsugu, Suzuki Shuhei, Seino Shizuka, Oizumi Hiroyuki, Sadahiro Mitsuaki, Kitanaka Chifumi
Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan.
Anticancer Res. 2016 Nov;36(11):6083-6092. doi: 10.21873/anticanres.11198.
GSKJ4, an H3K27 demethylase inhibitor, reportedly exhibits antitumor activity against specific cancers harboring genetic alterations in genes encoding chromatin modulators. However, its potential as an anticancer agent against human cancers not associated with such genetic alterations, including non-small cell lung cancer (NSCLC), remains unknown.
The effect of GSKJ4 on the growth of three NSCLC cell lines and normal lung fibroblasts was investigated using the WST-8, dye exclusion, and colony formation assays.
GSKJ4, alone and in combination with an anti-diabetic drug metformin, induced cell death and inhibited the growth of NSCLC cell lines efficiently at concentrations non-toxic to normal cells, irrespective of their genetic backgrounds (mutations in the KRAS, TP53 and EGFR genes) and also of their resistance to cisplatin and paclitaxel.
GSKJ4, being a promising anticancer agent for NSCLC, may be effective against a wider spectrum of cancers than previously thought.
据报道，H3K27去甲基化酶抑制剂GSKJ4对特定癌症具有抗肿瘤活性，这些癌症在编码染色质调节剂的基因中存在基因改变。然而，其作为抗癌药物针对包括非小细胞肺癌（NSCLC）在内的与此类基因改变无关的人类癌症的潜力仍不清楚。
使用WST-8、染料排除法和集落形成试验研究了GSKJ4对三种NSCLC细胞系和正常肺成纤维细胞生长的影响。
GSKJ4单独使用以及与抗糖尿病药物二甲双胍联合使用时，在对正常细胞无毒的浓度下能有效诱导细胞死亡并抑制NSCLC细胞系的生长，无论其基因背景（KRAS、TP53和EGFR基因的突变）如何，也无论其对顺铂和紫杉醇的耐药性如何。
GSKJ4作为一种有前景的NSCLC抗癌药物，可能对比以前认为的更广泛的癌症有效。
